AB0065 COMPARISON OF HISTOLOGICAL AND MOLECULAR FEATURES IN PATIENTS WITH AN ACTIVE RHEUMATOID ARTHRITIS AND PATIENTS IN REMISSION
Authors: S. Ohl, K. Frommer, M. Rickert, S. Rehart, U. Müller-Ladner, E. Neumann
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. The disease is manifested by inflamed synovium and destruction of cartilage and bone. So far, the disease cannot be cured, which is why remission is considered as the therapeutic goal. Although the number of patients in remission is increasing, patients still have different prognostic outcomes, which is why a better understanding of remission is needed. <h3>Objectives</h3> Characterization of remission in RA by comparison of histological and molecular features in the synovium of active RA patients compared to patients in remission. <h3>Methods</h3> After joint replacement surgery, RA patients between 43 and 81 years were clinically classified into either remission or active RA. Clinical classification was based on laboratory (e.g. ESR, CRP, leucocytes) and clinical parameters (e.g. painful joint, pain degree, medication). Subsequently, the Krenn Score was applied to characterize synovitis in the synovial tissue. To investigate remission on RNA level, RA synovial fibroblasts (RASF) from both patient groups were either stimulated with IL-1 or left unstimulated for 24h. RNA was isolated and analysed by RNA sequencing. Evaluation included analysis of differentially expressed genes (DEG) based on a combination of absolute expression, divergence and significance as well as gene set enrichment analysis of DEGs to identify the enriched gene sets or pathways. <h3>Results</h3> A total of 39 patients were included in the Krenn Score, of whom 20 were active and 19 in remission. Patients in remission showed a generally lower synovitis score for all parameters. In particular, a reduced synovial hyperplasia of the lining layer (<i>P</i>=0.021) and the total Krenn score (<i>P</i>=0.022) was observed. Sub-analyses regarding medication (biologics, DMARDs, NSAIDs, glucocorticoids) also showed a decreased hyperplasia for patients in remission, especially for patients who received biologics (4.2 fold decrease). Regarding the RASF, RNA sequencing showed a general homogeneity of the expressed genes and the underlying pathways between patients in remission and active RA patients. This observation was evident in both, the unstimulated approach and the stimulated RASF. However, RNAseq identified several DEGs including IL-36B (-7.14 fold) and the IL-36 receptor antagonist (-11.49 fold), cathepsin K (-1.66 fold) and folliculin (-1.54 fold), which were downregulated in patients in remission. <h3>Conclusion</h3> The histological analysis illustrates that patients in remission, especially patients receiving biologics, show a lower degree of inflammation and hyperplasia. RNAseq identified several genes showing altered gene expressions related to the diminished pro-inflammatory and destructive processes during RA. Of note, pro-inflammatory IL-36 family members were predominantly downregulated, which could be used as biomarker for remission. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.